PROJECT SUMMARY Early conductive hearing loss (eCHL) in children, arising from chronic ear infections, can induce long-lasting problems in auditory perception and language processing. When raised with environmental challenges, such as disrupted attachment and low socio-economic status, these children are at greater risk for long-term language deficits. One explanation is that early-life stress (ELS) and eCHL in conjunction could interact in the nervous system to produce compounded deficits in auditory perception. While ELS has well-known effects on higher neural regions involved in attention and learning, our evidence suggests a novel auditory effect for ELS: altering sound-evoked responses in the auditory cortex (ACx). This would degrade the fidelity of sensory representations available to higher regions affected by ELS, and could contribute to known cognitive problems with ELS. Such sensory degradation would compound the auditory perceptual issues arising from eCHL. The central hypothesis of this proposal is that ELS causes deficits in auditory perception, and worsens eCHL- induced deficits, by altering sensory representations in the central auditory system. We will measure effects of ELS on auditory perception and ACx sensitivity, and will determine whether altered inhibition in the auditory system contributes to measured deficits. Amplitude modulations (AM) in sounds will be used to determine perceptual and neural auditory sensitivity, because AMs are intrinsic to speech and animal vocalizations, and their accurate perception involves ACx. In Aim 1, we test whether ELS impairs auditory perception and compounds impairments from eCHL. Animals will be trained to detect AM sounds with varying parameters (modulation rate and depth). This will characterize the nature of the deficits by identifying AM parameters that are challenging for animals to detect when raised with ELS, eCHL, or both. In Aim 2, we test whether perceptual deficits arising from ELS and ELS+eCHL involve impaired sensory encoding in ACx. Neural responses while animals listen passively to AM sounds will indicate altered sensory representations. Task performance is known to increase ACx sensitivity by engaging additional non-sensory areas, including cognitive regions known to be altered by ELS. We will determine whether ELS impairs non-sensory contributions to auditory processing, by comparing ACx responses while animals are learning and performing the task versus listening passively to the same sounds. In Aim 3, we will determine if ELS and ELS+eCHL alter inhibition in ACx and other subcortical auditory regions, and whether inhibitory rescue improves ACx function and perception. This will identify mechanistic changes underlying ELS-eCHL effects. Together, these experiments will reveal the extent to which early-life stress impairs auditory processing via changing sensory and non-sensory regions. This will broaden our understanding of experiences that interact with hearing loss, and provide a focus for future experiments to determine in greater detail the mechanisms by which ELS may alter auditory function.